title: Non-neuronal cell responses differ between normal and Down syndrome developing brains.
abstract: Down syndrome (DS), the most common genetic cause of mental retardation, is characterized by reduced number of neurons and delayed myelination. Though non-neuronal cells in the brain are vital for the development, survival, and function of neurons, there is a paucity of comparative studies of normal development and DS, in particular in the temporal lobe, a region of interest for cognitive decline. We evaluated immunoreactivity for CD68 (macrophage), HLA-DR (microglia), Olig2 and TPPP/p25 (oligodendroglia), and GFAP (astroglia) in the germinal matrix (GM), temporal lobe white matter (TeWM) and hippocampus from 14 weeks of gestations to newborn in 28 DS patients and 30 age-matched controls. The rate of increase of CD68 positive cells in the GM, CA1 hippocampal subregion and subiculum was significantly higher in DS. The density of Olig2 positive cells in the GM was lower in DS brains at early stages, then showed a transient increase contrasting controls. Olig2 expression increased more in the TeWM in DS, suggesting an altered pattern of oligodendrocyte progenitor generation. GFAP-immunoreactivity in DS was significantly lower in the middle pregnancy period in the TeWM and did not increase between early and middle periods in the GM compared to controls, likely reflecting a defect in astrocyte production. The altered expression of non-neuronal cell markers during normal development and DS may play a role in, or reflect, defective neurogenesis, leading to reduced number of neurons and delayed myelination in the developing DS brain. This has implications for the understanding of the mental retardation in DS patients.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna A-1090, Austria; Department of Pediatrics, Nakatsu Municipal Hospital, Nakatsu 871-8511, Japan; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanaumi
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
mesh_terms: D000704:Analysis of Variance; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D002452:Cell Count; D000090266:Chromobox Protein Homolog 5; D004314:Down Syndrome / Q000473:pathology*; D005260:Female; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D000076104:Oligodendrocyte Transcription Factor 2; D011247:Pregnancy; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051792:Basic Helix-Loop-Helix Proteins; D000090266:Chromobox Protein Homolog 5; D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C000715594:CBX5 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C405708:OLIG2 protein, human; C118136:TPPP protein, human
keywords: CD68; Fetus; GFAP; HLA-DR; Human; Olig2; TPPP/p25